Association of Human Papillomavirus (Hpv) and P16 Status with Efficacy and Safety Data in the Phase III Radiotherapy (Rt)/Cetuximab (Cet) Registration Trial for Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck (Lascchn)

Abstract

ABSTRACT Aim: This is a retrospective analysis of the phase III IMCL-9815 trial assessing the role of HPV in LASCCHN patients (pts) receiving RT + cet or RT alone by measuring p16 expression and detecting HPV DNA. A strong correlation has been demonstrated between the presence of HPV DNA and p16 expression levels and thus p16 is a valuable marker as it may detect carcinomas associated with various HPV types for which in situ hybridization (ISH) probes are not yet available. This study aims to provide more evidence to clarify this relationship. Total test (n) Positive (n) % Negative (n) % Not evaluable (n) % p16 status 336 83 24.7% 228 67.9% 25 7.4% HPV status in p16+ LASCCHN 83 54 65.1% 15 18.1% 14 16.9% Methods: The intent-to-treat (ITT) population (424 pts) was randomized to RT + cet or RT alone. p16INK4A status was determined by immunohistochemistry and the presence of HPV DNA detected by ISH. We assessed the treatment outcomes by p16 status and HPV status. Results: 311/424 (73%) of the ITT pts were p16 evaluable, 83 (26.7%) were p16+. Of these, 69/83 (83%) were evaluable for HPV status, with 54/69 (78%) HPV+ and 15/69 (22%) HPV- (Table). In both p16+ and p16- pts, the addition of cet to RT improved locoregional control (LRC), overall survival (OS) and progression-free survival (PFS). Univariate analyses showed a more pronounced treatment effect of RT + cet vs RT alone in p16+ pts across all endpoints in both the ITT and the oropharyngeal (OPC) populations. Interaction tests for LRC, OS and PFS (ITT and OPC) did not demonstrate a significant interaction between p16 status and treatment effect. Outcome analyses and influence of p16 and HPV status on prognosis and mucositis/dysphagia data in the p16 and HPV evaluable subpopulations will be presented at the meeting. Conclusions: p16 tumor status is strongly prognostic for pts with LASCCHN. Although the number of pts is small, these data show that pts achieve an improved clinical outcome from RT + cet compared with RT alone regardless of p16 status. Disclosure: J.A. Bonner: Bristol-Myers Squibb Advisory Board Bristol-Myers Squibb Research Support; J. Liu: Salaried employee at Merck KGaA; J. Schulten: I am an employee of Merck Serono; D.I. Rosenthal: Merck-Serono advisory board. All other authors have declared no conflicts of interest.